Abstract: AIM: To explore the effects of prolonged sevoflurane exposure on prefrontal cortical metabolites in aged mice using a metabolomics approach.  METHODS: Ten 18-month-old male C57BL/J6 mice were divided into a sevoflurane group (Sev group) and a control group (Con group) by the random number table method, with five mice in each group. Mice in the sevoflurane group were anesthetized with 3%sevoflurane and 60%oxygen for 6 h. Mice in the control group were given 60%oxygen under the same conditions for 6 h. All mice were executed immediately after the end of anesthesia or oxygenation, and fresh prefrontal cortex was taken for LC-MS/MS analysis. The data obtained were processed and analyzed using OSV2.1 software (AB SCIEX). RESULTS: Compared with the control group, the content of glutathione, arginine, coenzyme A, 1-methyl-histidine, L-arginino-succinate and 2-isopropylmalic acid was reduced in the prefrontal cortex of aged mice in the sevoflurane group, while the content of mesaconic acid was increased. A total of 29 metabolic pathways were involved in the differential metabolites, with significant enrichment in nine pathways including arginine biosynthesis. CONCLUSION: Significant changes in metabolites such as glutathione, arginine, and coenzyme A occurred in the prefrontal cortex of aged mice exposed to prolonged sevoflurane. The changes in these products may affect the amino acid metabolic pathway and the gluconeogenic pathway.

Key words: metabolomics, sevoflurane, aged mice, prefrontal cortex